NAC

NAC

NAC: A Natural Product So Powerful It Is Used in Hospitals
2017-01-11 02:17:36
Gunda Siska, PharmD
Natural products are a hot topic these days. As a pharmacist, I am very impressed by a natural product called NAC, short for N-acetylcysteine. This pill is available to everyone and can be purchased at virtually any health food store or pharmacy. It's made by various manufacturers and ranges in price from $0.17 to $0.99 per pill depending on the milligrams.

In the hospital, it is used in the intravenous and oral form to protect and restore the body before and after it has been exposed to certain chemicals, including radioactive dyes used to illuminate parts of the body during an MRI, and in the case of acetaminophen overdose. Its also used sometimes to help cancer patients overcome the adverse events that may be associated with isoffamide and cyclophosphamide.

NAC is an immediate precursor to a very precious substance that our body makes. It's called glutathione. Amino acids such as cysteine, glutamate, and glycine are also natural precursors from the food we eat.

On Sept. 2, 2015, the FDA tweeted that IV glutathione was being used as a skin lightener. It restores the skin to the color of early childhood. It is not approved for use here in the United States and the FDA cautioned that the products from outside the country were being confiscated.1 The only products on the market here in the United States are the oral and topical skin formulations or glutathione and NAC. Several oral liquid formulations of NAC have specifically marketed products to mask the unpalatable sulfur taste. The unadulterated liquid formulation can be very reminiscent of rotten egg juice.

Foods high in glutathione precursors are broccoli, cauliflower, and asparagus. Vegetables with a high sulfur content yield naturally high glutathione levels.

For people who believe they need more than what their diet can provide, NAC can be purchased in pill forms ranging from 300 to 900 mgs. Twice daily administration or three times daily administration is commonly recommended by the manufactures.

There is no recommended daily allowance for NAC, because unlike vitamins, its not an essential nutrient.

The dosage used to prevent radio contrast dye damage is 600 mg to 1200 mg every 12 hours for 48 hours.

Oral doses above 1200 mg per day can result in headache, nausea, abdominal pain, vomiting, constipation, and diarrhea.

People who take nitroglycerine should not take NAC unless supervised by a physician since it can cause the nitroglycerine to work more intensely and cause an unsafe drop in blood pressure.

In the hospital setting, the use of NAC yields potential benefits that outweigh the potential risks. Glutathione levels are being restored and maintained in the normal range because the toxins deplete glutathione.

Drug studies have measured the glutathione levels going down after the toxic exposure. Damage to the body and vital organs occur, usually involving the liver or kidneys depending on the toxic exposure. Studies have also measured glutathione levels going up after NAC administration and damage to vital organs is mitigated.2, 3, 4

In the skin lightening situation, normal glutathione levels are being elevated even higher. This is usually when good pills do bad things. The risk-benefit ratio is no longer the same. Treating a healthy person is very different than treating a sick person. Medical professionals take a vow never to cause harm and giving medicine to a healthy person is not the same as giving medicine to a sick person.

Vitamin C is similar to glutathione in that it is also a powerful antioxidant depleted by toxins. Smoking tobacco depletes vitamin C levels and the expert doctors at the National Institute of Health (NIH) have recommended that healthy smokers consume extra vitamin C supplement in the pill form.5 According to their website they recommend a dose of vitamin C 35 mg every day. Its a small dose, but enough to restore the vitamin C levels to normal.

Interestingly, vitamin C is also used in the IV form as a skin lightener, often times it is combined with glutathione.

Could glutathione and its precursors be a key in slowing the aging process? Do high levels restore and repair damage that has already occurred? That is being investigated now. It might be too soon to recommend glutathione and its immediate precursors, but the data are coming in fast, thanks to the internet, newsletters, and databases.

Stay tuned, and I will keep you updated. Until then, eat lots of broccoli, cauliflower, and asparagus.

N-acetylcysteine Can Be Beneficial for Bronchiectasis ...
https://bronchiectasisnewstoday.com/2019/05/09/n-acetylcysteine-potentially-beneficial...
May 09, 2019 Treatment with N-acetylcysteine, a mucus-dissolving and anti-inflammatory agent, reduces the frequency of acute worsening episodes and improves the quality of life of patients with bronchiectasis, results from a randomized trial in China show.

N-Acetyl Cysteine (Nac): Uses, Side Effects, Interactions ...
https://www.webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine
Taking N-acetyl cysteine by mouth seems to decrease flare-ups by about 40% and improve sputum (phlegm) consistency in people with moderate to severe COPD. It

Acetylcysteine - The official site for Acetylcysteine ...
https://acetylcysteine.com
WHAT IS Acetylcysteine? Acetylcysteine is a mucolytic (medicine that destroys or dissolves mucus). It is usually given by inhalation but may be given in other ways in a hospital. This medicine is used for certain lung conditions when increased amounts of mucus make breathing difficult.

Role of N-acetylcysteine in the management of COPD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2707813
N-acetylcysteine is a thiol compound which has a chemical formula C 5 H 9 NO 3 S and a molecular weight of 163.2. It is rapidly absorbed following an oral dose of 600 mg with a peak of 4.6 M after 60 min (Tsikas et al 1998).

Cited by: 89
Publish Year: 2006
Author: Sadowska Am, Verbraecken J, Darquennes K, De B


Aerosolized Administration of N-Acetylcysteine Attenuates Lung Fibrosis Induced by Bleomycin in Mice


SHIN-ICHI HAGIWARA , YOSHIKI ISHII , and SATOSHI KITAMURA
https://doi.org/10.1164/ajrccm.162.1.9903129 PubMed: 10903246
Received: March 26, 1999


Abstract

Reactive oxygen species (ROS) play an important role in the pathogenesis of pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), an antioxidant, inhibited adhesion molecule expression and cytokine production in lung cells. When NAC is inhaled into the alveolar space, it is expected to directly interact with inflammatory cells and to elevate glutathione levels in the epithelial lining fluids. We therefore examined whether inhaled NAC inhibits lung fibrosis induced by bleomycin (BLM). Male ICR mice were given a single intravenous injection of BLM (150 mg/ kg). Thirty milliliters of NAC (70 mg/ml) or saline were inhaled twice a day for 28 d using an ultrasonic nebulizer. In the inflammatory phase (Day 7), NAC administration attenuated the cellular infiltration in both bronchoalveolar lavage fluid (BALF) and alveolar tissues. At Day 28, the fibrotic changes estimated by Aschroft's criteria and hydroxyproline content in the NAC inhalation group were significantly decreased compared with the BLM-only group (p < 0.05). CXC chemokines, macrophage inflammatory protein-2 (MIP-2), cytokine-induced neutrophil chemoattractant (KC), and CC chemokines, macrophage inflammatory protein-1 (MIP-1 ), in BALF were mostly elevated on Day 7 in the BLM-only group; however, these elevations were significantly repressed by NAC inhalation (p < 0.05). Lipid hydroperoxide (LPO) was also quantified in BALF. LPO was markedly increased on Day 3 in the BLM-only group, and this increase was significantly decreased by NAC inhalation (p < 0.05). These results revealed that aerosolized NAC ameliorated acute pulmonary inflammation induced by BLM injection via the repression of chemokines and LPO production, resulting in the attenuation of subsequent lung fibrosis. These findings are limited to the BLM-induced lung fibrosis animal model. However, NAC inhalation will be expected to be a potential therapy for patients with other interstitial pneumonias because ROS are involved in the pathogenesis of lung injury in most interstitial pneumonia.

Fibrosis is a reactive or reparative process characterized by the formation of excessive fibrous tissue. In the lung, inflammation and immune processes are the major pathogenic mechanisms that injure tissue and stimulate fibrosis (1). There is considerable evidence that oxygen-generated free radicals play a major role in inflammatory and immune-mediated tissue injury (2-4).

Bleomycin (BLM) is an antineoplastic agent. The mechanism of the antineoplastic effect of BLM is that the BLM-iron complex reduces molecular oxygen to superoxide and hydroxy radicals that can then attack DNA and cause strand cleavage (5). The role of oxygen free radicals has been supported by studies showing that the addition of superoxide dismutase, an oxygen free radical scavenger, inhibits BLM-induced DNA breakage and cellular damage in vitro (6, 7). On the other hand, BLM induces pulmonary fibrosis as an adverse effect since the hydrolase that inactivates BLM is relatively scarce in lung tissue. Therefore, a BLM-induced pulmonary fibrosis model in mice is a helpful tool to examine the general mechanism of fibrosis, especially that mediated by oxygen free radicals.

Oxidants produced by inflammatory cells are considered to play a role in lung injury in idiopathic pulmonary fibrosis (IPF). Antioxidants are decreased in bronchoalveolar lavage (BAL) from patients with IPF since the level of glutathione (GSH) was found to be approximately one third of the normal concentration (8). It is possible to raise the level of GSH in bronchoalveolar lavage fluid (BALF) in patients with IPF by aerosol administration of GSH, and the release of oxidants by cells isolated from the BAL was found to be decreased by aerosolized GSH (9).

N-acetylcysteine (NAC) is not only a precursor of GSH but also shows a direct scavenging ability of oxygen free radicals (10, 11). Moreover, it regulates the production of some cytokines or the expression of adhesion molecules on endothelial cells and bronchial epithelial cells. On the basis of these findings, the effectiveness of NAC administration on animal models of lung fibrosis has been reported (12-14). Recently, Behr and colleagues (15) reported that oral high dose administration of NAC with low dose oral steroids to patients with IPF significantly improved the lung function index. However, NAC does not produce a sustained increase in GSH levels sufficient to increase the antioxidant capacity of the lungs, even when given in high oral doses (16). Furthermore, NAC itself is not detected in BALF nor in lung tissue when given orally (17). In contrast, aerosol administration of NAC directly act as an antioxidant in alveoli in addition to the GSH increasing effect. Therefore, aerosolized NAC may attenuate the inflammation and lung fibrosis more effectively.

We examined here whether aerosol NAC administration inhibited lung inflammation and fibrosis induced by BLM injection in mice. Moreover, to evaluate the inhibitory mechanisms, the levels of chemokines and lipid hydroperoxide (LPO) in BALF were measured and compared among the study groups.

In conclusion, NAC inhalation showed an inhibitory effect on BLM-induced acute inflammation after pulmonary fibrosis. The effect was limited when NAC was administered in the acute inflammatory phase. This may be due to the inhibition of chemokine production or scavenging of reactive oxygen radicals by NAC itself. NAC is largely free of adverse effects and has been used for many years as a mucolytic agent by direct instillation or nebulization into the airway (44). Although our findings are limited to the BLM-induced animal model, NAC inhalation is expected to be a potential therapy for other interstitial pneumonia because ROS are involved in the development of almost all interstitial pneumonia.

Aerosolized Administration of N-Acetylcysteine Attenuates Lung Fibrosis Induced by Bleomycin in Mice | American Journal of Respiratory and Critical Care Medicine
https://www.atsjournals.org/doi/full/10.1164/ajrccm.162.1.9903129

Uses for acetylcysteine

Acetylcysteine is a mucolytic (medicine that destroys or dissolves mucus). It is usually given by inhalation but may be given in other ways in a hospital.

Acetylcysteine is used for certain lung conditions when increased amounts of mucus make breathing difficult. Acetylcysteine liquefies (thins) or dissolves mucus so that it may be coughed up. Sometimes the mucus may have to be removed by suction.

Acetylcysteine is available only with your doctor's prescription.

Acetylcysteine Inhalation, oral/nebulization Advanced Patient Information - Drugs.com
https://www.drugs.com/cons/acetylcysteine-inhalation-oral-nebulization.html

Clarithromycin and N-acetylcysteine co-spray-dried powders for pulmonary drug delivery: A focus on drug solubility

Author links open overlay panelMichele DarioMannielloabPasqualeDel GaudioaRita P.AquinoaPaolaRussoa
a
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy
b
PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy


Abstract
Cystic fibrosis (CF) lungs are usually susceptible to Pseudomonas aeruginosa colonization and this bacterium is resistant to immune system clearance and drug control. Particularly, the biofilm mode of growth protects several microorganisms from host defenses and antibacterial drugs, mainly due to a delayed penetration of the drug through the biofilm matrix. Biofilm, together with lung mucus viscosity and tenacity, reduces, therefore, the effectiveness of conventional antibiotic therapy in CF. The aim of this research was to design and develop a stable, portable, easy to use dry powder inhaler (DPI) for CF patients, able to release directly to the lung an association of macrolide antibiotics (clarithromycin) and a mucolytic agent (N-Acetyl-Cysteine). Its effectiveness is based on the counteracting of the characteristics of P. aeruginosa infections in CF (lung bacterial adhesion to lung epithelium, biofilm formation and mucus viscosity) and the ability to let the antimicrobial drug exert their pharmacological action.

A solution of these two drugs, without any excipients, was spray-dried to obtain respirable microparticles, characterized by aerodynamic diameters suitable for inhalation (<5.0 m). The morphology evaluation evidenced particles shape dependent on water content in the spray drying feeds, with wrinkled particles more evident with higher water content. Moreover, thanks to the presence of N-acetylcysteine which can interact with clarithromycin dimethyl-amino group, a consistent enhancement of drug solubility was obtained, compared to raw material and to the drug sprayed alone. The mucolytic agent added in the DPI may improve the macrolide diffusion into the mucus, enabling its action.

Clarithromycin and N-acetylcysteine co-spray-dried powders for pulmonary drug delivery: A focus on drug solubility - ScienceDirect
https://www.sciencedirect.com/science/article/pii/S0378517317302661